Sesquiterpenoids isolated from the flower buds of Tussilago farfara L. inhibit diacylglycerol acyltransferase.
Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT), which is a key enzyme in triglyceride synthesis in eukaryotic organisms, has been proposed as one of the drug targets for treating obesity, type II diabetes mellitus, and metabolic syndrome. Bioassay-guided fractionation of EtOH extract of the flower buds of Tussilago farfara , using an in vitro DGAT enzyme assay, resulted in the isolation of four known sesquiterpenoids, tussilagonone (1), tussilagone (2), 7beta-(3-ethyl-cis-crotonoyloxy)-1alpha-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (3), and 8-angeloylxy-3,4-epoxy-bisabola-7(14),10-dien-2-one (4). DGAT1 inhibitory activity was studied by in vitro DGAT assay using rat liver microsomes and HepG2 cell microsomes. They showed DGAT1 inhibition with IC(50) values of 99.2 (1), 18.8 (2), 47.0 (3), and 211.1 (4) microM (for rat liver microsomes) and >1 mM (1), 49.1 (2), 160.7 (3), and 294.4 (4) microM (for HepG2 cell microsomes), respectively. Compound 2 showed the most potent inhibition against microsomal DGAT1 derived from rat liver and human hepatocellular carcinoma HepG2 cells and also significantly inhibited triglyceride synthesis by suppressing incorporation of [(14)C]acetate or [(14)C]glycerol into triglycerides in HepG2 cells. These findings suggest that tussilagone is a potential lead compound in the treatment of obesity and type 2 diabetes.
Park
Hye Ran
HR
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Yoo
Mi Young
MY
Seo
Jee Hee
JH
Kim
Il Soon
IS
Kim
Nam Ye
NY
Kang
Ji Yun
JY
Cui
Long
L
Lee
Chang-Soo
CS
Lee
Chul-Ho
CH
Lee
Hyun Sun
HS
D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry*; D006801:Humans; D008113:Liver Neoplasms; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology*; D014280:Triglycerides / Q000096:biosynthesis; D031207:Tussilago / Q000737:chemistry*
D004791:Enzyme Inhibitors; D012717:Sesquiterpenes; D014280:Triglycerides; D051048:Diacylglycerol O-Acyltransferase